AVP also increases the permeability of the terminal portion of the inner medullary collecting duct to urea. This results in an increase in urea reabsorption and an increase in the osmolality of the medullary interstitial fluid, which as described below is needed for maximal urine concentration. The cells of the collecting duct express two types of urea transporters, UT-A1 and UT-A3. UT-A1 is localized to the apical membrane, and UT-A3 is localized primarily to the basolateral membrane. AVP, acting through the cAMP/PKA cascade, increases expression of both UT-A1 and UT-A3. Increasing the osmolality of the interstitial fluid of the renal medulla also increases the permeability of the inner medullary collecting duct to urea. This effect is mediated by the phospholipase C/protein kinase C (PKC) pathway, which increases UT-A1 and UT-A3 expression.
AVP also stimulates reabsorption of NaCl by the thick ascending limb of Henle’s loop and by the distal tubule and cortical segment of the collecting duct. This increase in Na+ reabsorption is associated with increased abundance of three Na+ transporters: the 1Na+/1K+/2Cl− symporter (thick ascending limb of Henle’s loop), the Na+/Cl− symporter (distal tubule), and the Na+ channel (ENaC, in the latter portion of the distal tubule and collecting duct). Stimulation of thick ascending limb NaCl transport may help maintain the hyperosmotic medullary interstitium that is necessary for absorption of water from the medullary portion of the collecting duct (see below).
In addition to affecting the secretion of AVP, changes in plasma osmolality and blood volume or pressure lead to alterations in the perception of thirst. When body fluid osmolality is increased or the blood volume or pressure is reduced, the individual perceives thirst. Of these stimuli, hypertonicity is the more potent. An increase in plasma osmolality of only 2% to 3% produces a strong desire to drink, whereas decreases in blood volume and pressure in the range of 10% to 15% are required to produce the same response.
As already discussed, there is a genetically determined threshold for AVP secretion (i.e., a body fluid osmolality above which AVP secretion increases). Similarly there is a genetically determined threshold for triggering the sensation of thirst. However, the thirst threshold is higher than the threshold for AVP secretion. On average the threshold for AVP secretion is approximately 285 mOsm/kg H2O, whereas the thirst threshold is approximately 295 mOsm/ kg H2O. Because of this difference, thirst is stimulated at a body fluid osmolality where AVP secretion is already maximal.
The neural centers involved in regulating water intake (the thirst center) are located in the same region of the hypothalamus involved with regulating AVP secretion. However, it is not certain whether the same cells serve both functions. Indeed the thirst response, like the regulation of